Porous membranes are used for a variety of applications. Porous membranes have a first porous surface, a second porous surface, and a continuous porous structure that extends throughout the membrane from the first to the second surface. The continuous porous structure includes the bulk material matrix and the network of pores. The interface separating the bulk matrix from the pore volume (i.e., the surface of the interior pore network) is known as the interstitial surface. The distance from the first surface to the second surface defines the membrane thickness. Depth is used herein to mean the perpendicular distance from one surface towards the other surface.
Herein, the term “facial surface” shall mean either or both of the first surface or the second surfaces. When discussing surface modifications, “surface” or “surfaces” shall mean both facial and interstitial surfaces.
Porous membranes can be classified as microporous membranes or ultrafiltration membranes on the basis of the size of the pores of the membrane. Generally, the range of pore sizes for microporous membranes is considered to be from approximately 0.05 micron to approximately 10.0 microns, whereas the range of pore sizes for ultrafiltration membranes is considered to be from approximately 0.002 micron to about 0.05 micron. These pore sizes refer to pore diameter for circular or approximately circular pores, or to a characteristic dimension for non-circular pores.
The pore size of a membrane can be denominated by the size of the smallest species (particle or molecule) that cannot pass through the membrane above a specified fractional passage. A common rating is below 10% passage, which corresponds to a 90% cutoff or retention. Other methods are known to those skilled in the art, including image analysis of scanning electron microscopy to obtain pore size distribution characteristics. Microporous membranes are typically used to remove particulates from liquids and gases. An important application of microporous membranes is in sterile filtration of pharmaceutical solutions to remove any bacteria that may be present in the solution. Microporous membranes are also used as sterile gas vents, which allow gas flow but prevent airborne bacteria from passing through the filter. Ultrafiltration membranes are generally used in applications where retention of smaller species is desired. For example, ultrafiltration membranes are used in the biotechnology industry to concentrate proteins, and in diafiltration applications to remove salts and low molecular weight species from protein solutions. Both ultrafiltration and microporous membranes can be fabricated in several forms, including sheets, tubes, and hollow fibers.
Porous membranes are made from a variety of materials, polymers being the most common. Many commercial membranes are made from engineering plastics, such as polyethersulfone, polysulfone, polyvinylidene fluoride, polyethylene, polytetrafluoroethylene, perfluorinated thermoplastic polymers such as poly(tetrafluoroethylene-co-perfluoro(alkylvinylether)) (POLY(PTFE-CO-PFVAE)) or poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP), polypropylene and so forth, to take advantage of their robust thermal, mechanical, and chemical-resistance properties.
Microporous membranes may be classified as symmetric or asymmetric, referring to the uniformity of the pore size across the thickness of the membrane. In the case of a hollow fiber, this is the porous wall of the fiber. Symmetric membranes have essentially uniform pore size across the membrane cross-section. Asymmetric membranes have a structure in which the pore size is a function of location through the cross-section. Another manner of defining asymmetry is the ratio of pore sizes on one surface to those on the opposite surface.
Membrane manufacturers commonly modify the membrane surface (i.e., the first and second surfaces and the interstitial surface) of the bulk matrix material making up the porous membrane to improve the performance of the membrane. For example, U.S. Pat. No. 4,618,533, issued to Michael J. Steuck on Oct. 21, 1986, discloses and claims a composite porous thermoplastic membrane which comprises a porous membrane substrate having an average pore size between about 0.001 and 10 microns formed of a first polymer, the substrate being directly coated on its entire surface with a cross-linked second polymer formed from a monomer polymerized in situ with a free radical initiator on the substrate, where the composite porous membrane has essentially the same porous configuration as the membrane substrate. Such processes are used to transform a membrane having hydrophobic surfaces, which bind large quantities of protein in use, into a membrane having hydrophilic surfaces, which allow self wetting and have low protein binding properties.
Other modified membranes are made to increase the hydrophobicity of the membrane surfaces. U.S. Pat. Nos. 5,217,802 and 5,554,414 describe methods of forming a polymerized coating of a cross-linked second polymer such that it does not wet with a solvent having a surface tension greater than about 21 mN/m. U.S. Pat. App. Pub. No. 2002/0139095 describes oleophobic membranes made by forming a polydimethylsiloxane coating on the surface of a filtration substrate. U.S. Pat. App. Pub. No. 2002/00144595 describes oleophobic and hydrophobic filters made by forming a florosulfone coating on the surface of a filtration substrate. Such membranes are useful for vents.
Methods of membrane modification that use free radical initiated copolymerized coatings have proven to be commercially successful. These methods, exemplified by the teachings of U.S. Pat. No. 4,618,533, have been successfully used to produce a variety of products. Such methods do not significantly change the pore size of the base membrane, and can be used to produce a variety of surface properties, e.g., hydrophilic, hydrophobic, ionic charge, etc.
The examples given above are typical of the multitude of ways membrane manufacturers modify membranes. They have in common that these methods modify all the surfaces of a membrane. Methods of modifying a membrane to a controlled depth from one surface are much less numerous.
Membranes modified to a controlled depth have utility in, for example, 96 well devices for protease assays. MultiScreen DP assay systems from Millipore Corporation (Bedford, Mass.) incorporate a hydrophilic microporous membrane with one facial surface treated to be hydrophobic. The DP membrane plates are recommended for small total volume (<50 μl) and protease assays, particularly for optical detection of filtrates, especially after prolonged (72 hrs.) incubation. The study of enzyme activity by precipitation assays, in which reagents are incubated, precipitated, washed, and counted, have widespread acceptance. Precipitation techniques simultaneously stop the enzyme reaction and precipitate (insolubilize) the enzyme.
A general procedure for such an assay includes the following steps when using, for example, a 96 well plate device:    1. Add a liquid containing the enzyme sample and reagents to plate wells.    2. Incubate (for enzyme reaction).    3. Add precipitation agent (usually trichloroacetic acid [TCA], typically 5% final concentration) to stop reaction and precipitate proteins.    4. Incubate at 4° C. or on ice.    5. Wash the unreacted, or free, components away. (Collect if needed to quantitate free.)    6. Count precipitate (bound on filter) and/or filtrate (free).
To conduct small volume assays, a membrane having a hydrophilic layer and a hydrophobic layer is especially useful. The liquid sample is applied to and held in the hydrophilic (top) layer during incubation. The bottom hydrophobic layer prevents leakage until a vacuum or pressure force is applied to overcome the hydrophobic force preventing permeation or leakage.
Methods of modifying a facial surface are known.
U.S. Pat. No. 5,468,390, issued to Crivello et al. on Nov. 21, 1995, describes a process for modifying aryl polysulfone membranes by placing an aryl polysulfone membrane into the presence of a hydrophilic vinyl monomer dissolved in a solvent and without any sensitizer or free radical initiator; and exposing the membrane to nonionizing ultraviolet light for a selected period of time for modifying the membrane by chemical grafting and attachment of the monomer at the surface of the membrane by covalent bonding without any sensitizer or free radical initiator. In a related paper (J. Membrane Sci. 105 (1995) 237-247) the authors show that the depth of modification from the facial surface exposed to the ultraviolet light is an excessively long processing time for a commercial process. In addition, ultraviolet light damages aryl sulfone polymer membranes, and such lengthy times would cause excessive damage to the porous structure of the membrane.
U.S. Pat. App. Pub. No. 2002/0155311, filed by Mayes et al. on Dec. 5, 2001, discloses membranes with (facial) surfaces having desired chemical functionality created by surface segregation of a branched component blended with a compatible matrix base component, the branched component having the desired functionality. The patent application is directed to articles having a hydrophobic core material with a hydrophilic surface. No discussion is given, nor contemplated about controlling the depth of modification. Furthermore, the technique is limited to blends of compatible polymers, with one polymer being capable of being entropically driven to the surface.
U.S. Pat. No. 5,369,012, issued to Koontz et al. on Nov. 29, 1994, discloses a portion of an organic polymer article such as a membrane is made hydrophilic by exposing a hydrophobic surface of the article to a depth of about 50 to about 5000 angstroms to atomic oxygen or hydroxyl radicals at a temperature below 100° C., preferably below 40° C., to form a hydrophilic uniform surface layer of hydrophilic hydroxyl groups. This appears directed to the modification of the facial surface, termed “external” in the patent, of non-porous membranes. The very thin modified depth is indicative of this because the vacuum based plasma technology used would immediately penetrate a porous membrane. Also, this process does not produce a free radical polymer coating, but reacts with the base polymer of the membrane. Such reactions generally degrade the physical properties of the polymer.
Somewhat related technology is described in U.S. Pat. No. 5,141,806, issued to S. L. Koontz on Aug. 25, 1992. In the patent, a microporous structure with layered interstitial surface treatments is prepared by sequentially subjecting a uniformly surface-treated structure to atomic oxygen treatment to remove an outer layer of surface treatment to a generally uniform depth, and then surface treating the so exposed layer with another surface treating agent.
As described in U.S. Pat. No. 5,141,806, all surfaces of a porous particle are uniformly treated with a first agent. The uniformly treated particle is then subjected to oxidation with atomic oxygen and/or hydroxyl radicals to remove the surface treating agent from an outer layer of the interstitial (and facial) areas leaving an inner region or layer modified with the first treating agent.
The disclosures and examples of this reference are directed to inorganic silica particles. It is unlikely that polymeric membranes could withstand the oxidation conditions used to remove the treatment without suffering damage to its structure. Further, this process could not be used with asymmetric membranes, as any damage to the fine pore retentive region of the pore size gradient characteristic of asymmetric membranes would destroy the membrane's utility.
U.S. Pat. App. Pub. No. 2002/0189455, filed by Lamon et al. on May 1, 2001, describes oleophobic coated membranes. The disclosure relates to oleophobic filtration media including polymeric membranes and other substrates that are coated with polymerized substituted or unsubstituted para-xylenes. The coating material of preferred embodiments is derived from one or more para-xylene dimers. The dimer in powder form is converted to a gaseous monomer that condenses and polymerizes on substrates at room temperature, forming a parylene coating.
Poly-para-xylene is generally applied to the substrate using a vacuum application system. A para-xylene dimer powder is typically placed in a vacuum system vaporization chamber and is heated to a temperature above 150° C. to convert the powder into vapor form. Next, the dimer in vapor form may be converted in a pyrolysis chamber to reactive para-xylene vapor via pyrolysis at 650° C. The reactive vapor may then be transferred to a polymerization chamber containing the membrane to be coated. The polymerization chamber may be maintained at ambient temperature. The reactive vapor typically polymerizes on the surface of the substrate, forming a uniform parylene coating
In a preferred embodiment, deposition of the parylene layer is controlled so as to only partially coat the substrate. For example, a parylene coating may be applied on a membrane on one surface only in a layer not fully penetrating the pores through the entire thickness of the membrane. The parylene layer may also be deposited in a “polka dot” geometry on a substrate. A “polka dot” geometry is defined as a generally regular array of areas having a circular or other shaped profile including deposited parylene and separated from each other by areas of bare substrate with no deposited parylene.
This method is limited to para-xylene polymers, and cannot be adapted to free radical polymerized polymers. Also, since it relies on condensation of the vaporous monomer onto the surfaces, which will occur from the facial surface into the interstitial region, the facial and outer regions will necessarily be more heavily coated, which will tend to plug the surface pores, particularly for small pore membranes, reducing permeability.
The single-film bipolar membranes disclosed in U.S. Pat. No. 4,140,815, issued to Dege et al. on Feb. 20, 1979) comprise a matrix of a polymeric film in intimate dispersed relationship with a relatively high amount of an aromatic polymer, which is suitably cross-linked such as with a di- or poly-functional compound. Highly dissociable cation exchange groups are chemically bonded to the aromatic nuclei from one side of the film, while highly dissociable anion exchange groups are subsequently chemically bonded to the remaining aromatic nuclei on the opposite side. The membrane so composed functions as a durable water-splitting membrane to generate acid and base from dissolved salts by electrodialysis. Such single film bipolar membranes are prepared from pre-swollen films containing a relatively high amount, i.e., at least 15% of an insoluble cross-linked aromatic polymer. Under controlled conditions, highly dissociable cationic-exchange groups are chemically bonded to the aromatic nuclei to a desired depth of the film from one side only; subsequently, highly dissociable anion-exchange groups are chemically bonded to the unreacted aromatic nuclei on the other side of the film. Bipolar membranes are by their nature non-porous.
Accordingly, there is a need for a method to modify porous membranes to a predetermined depth form one facial surface with free radical polymerized polymer coatings. Furthermore, there is a need for integral membrane products having a functional modification on surfaces of a predetermined and controlled region of the interstitial volume, including one facial surface. An integral membrane has a unified structure, such as a single sheet or hollow fiber membrane. This also includes composite membranes, such as described in U.S. Pat. No. 4,824,568, and membranes, such as described in PCT Pat. App. Pub. No. WO 0189673.
For ease of description, the predetermined and controlled region of the interstitial volume, usually including one facial surface, will be termed herein a “a layer”.
There is also a need for modified membranes having a desired surface pattern where the modification is prevented from forming, and with this prevention being extended to a controlled depth into the membrane.